Recombinant interferon α‐2A combined with prednisone in metastatic renal‐cell carcinoma: Treatment results, serum interferon levels and the development of antibodies

Abstract

Five partial responses were seen in 23 patients with metastatic renal-cell carcinoma (MRCC) receiving interferon-alpha 2a (IFN)+prednisone (P). Four of 24 subsequent patients responded to IFN+P (combined response rate 19%). The median response duration was 8 months (3 to 30 months). The one-year survival for all eligible patients was 52%. Eight of 26 evaluable patients developed antibodies detected by an enzyme immunoassay. In 2 patients, high levels of neutralizing antibodies were also found, together with particularly low IFN levels. In one patient the development of neutralizing antibodies coincided with the loss of initial response. The treatment was well tolerated by most patients. Premature discontinuation of treatment was necessary in only 2 patients. In MRCC, combination treatment with IFN+P is as effective as IFN monotherapy (response rate 19%), with significantly reduced subjective toxicity. The clinical relevance of the development of antibodies against IFN requires further investigation.

Unexpected 10 years complete remission after cortisone mono-therapy in metastatic renal cell carcinoma

“…Immune mechanisms are most often evoked as the mechanism of regression [2]. Interferon-a and Interleukin-2 have been shown to exert antitumour effects in a subset of patients with MRCC [2,8]. Interleukin-2 is presumed to activate T-lymphocytes, natural killer (NK) cells, lymphocyte-activated killer cells and tumour infiltrating lymphocyte cells as a mechanism of action.…”

“…The necrotic areas in our patient's metastases before any therapy may indicate some degree of treatment-independent initiation of tumour regression. In this connection it is interesting that patients with MRCC respond to treatment with interferon-a even though the drug is combined with prednisone [8]. The role of glucocorticoids is therefore undefined in MRCC.…”

Dexamethasone and interleukin‐2 combination therapy for advanced renal cell carcinoma in a patient with paraneoplastic inflammatory syndrome

“…reported that a combination treatment with interferon and prednisone for patients with metastatic renal cell carcinoma showed a similar response rate to interferon monotherapy, with significantly reduced subjective toxicity. 9 This is likely to apply to other immunotherapeutic agents, but it has not been demonstrated yet. Moreover, only very few cases have been reported in which steroids manifested antitumor effects against renal cancer in clinical settings.…”

Immunogenicity of recombinant human proteins: causes and consequences

“…Both are nonglycosylated recombinant proteins but differ in the amino acid at position 23: lysine in IFNα-2a and arginine in IFNα-2b. The incidence of antibody production has been reported to be higher in patients who receive IFNα-2a compared with patients who receive IFNα-2b [26].As shown in Table 1, studies have reported that from 19 % to 61 % of patients develop NAbs to IFNα-2a [4,11,13,14,26,30,33,37].…”